DESCRIPTION: Diets rich in fatty acids of the n-3 family have positive health benefits in man including reduced cardiovascular problems and cancer incidence. There is some data to suggest that n-3 fatty acids are essential for normal human growth and development although the specific role played by n-3 fatty acids in cellular activities is completely unknown. The applicants have obtained evidence that docosahexaenoic acid (C22:6 n-3, DHA) has a direct effect on gene transcription in HL-60 cells, a human promyelocytic leukemia cell line. The effects of DHA include growth arrest, increased cell differentiation, and the disappearance of the c-myc proto-oncogene message. At higher concentrations DHA induces apoptosis in HL-60 cells, and might prove to be of considerable therapeutic value. It is their hypothesis that DHA affects cellular programs of differentiation and apoptosis by having an impact on gene transcription and entering signal transduction pathways. The projects described in this application are designed to test that hypothesis by; (1) determining what effects DHA has on programs of differentiation; (2) determining the effects of DHA on guanine nucleotide binding proteins (G-proteins); (3) determining which signal transduction pathways DHA participates in; and (4) determining the mechanisms by which DHA induces apoptosis.